Non-invasive visualization of amyloid-beta deposits in Alzheimer amyloidosis mice using magnetic resonance imaging and fluorescence molecular tomography

One of the major hallmarks of Alzheimer′s disease is the abnormal cerebral accumulation of amyloid-beta. Non-invasive monitoring of amyloid-beta deposits enables monitoring of treatment effects and understanding of the disease mechanism in the brain of disease animal models. Previous fluorescence imaging of has been mainly based on 2D diffuse fluoresence imaging and two-photon imaging with small field-of-view. Here we utilized a magnetic resonance imaging (MRI) and fluorescence molecular tomography (FMT) pipeline assisted with curcumin derivative CRANAD-2 for detecting the amyloid-beta; accumulation in arcAb mouse model of Alzheimer amyloidosis in 3D. A homebuilt FMT system was used for data acquisition, and a customized software platform was employed to enable the integration of anatomical information from MRI for assisting the FMT image reconstruction. To validate the multi-modal FMT-MRI method, conventional fluorescence reflectance imaging was conducted in the same conditions. Concordance in the time course of fluoresence intensity after intravenous injection of CRANAD-2 in the brain was observed. In conclusion, we have demonstrated the feasibility of visualizing amyloid-beta; deposition in 3D using a multi-modal MRI-FMT method. This multimodal imaging method can provide complementary information of anatomical and molecular information thus facilitating future mechanistic studies and monitoring of putative treatments targeting amyloid-beta; in disease animal models.

Intravital mesoscopic fluorescence molecular tomography allows non-invasive in vivo monitoring and quantification of breast cancer growth dynamics

Preclinical breast tumor models are an invaluable tool to systematically study tumor progression and treatment response, yet methods to non-invasively monitor the involved molecular and mechanistic properties under physiologically relevant conditions are limited. Here we present an intravital mesoscopic fluorescence molecular tomography (henceforth IFT) approach that is capable of tracking fluorescently labeled tumor cells in a quantitative manner inside the mammary gland of living mice. Our mesoscopic approach is entirely non-invasive and thus permits prolonged observational periods of several months. The relatively high sensitivity and spatial resolution further enable inferring the overall number of oncogene-expressing tumor cells as well as their tumor volume over the entire cycle from early tumor growth to residual disease following the treatment phase. Our IFT approach is a promising method for studying tumor growth dynamics in a quantitative and longitudinal fashion in-vivo.